The growth in treatments for RA and arthritis has also benefited lupus patients with concurrent RA or arthritis issues, Dr. Schur says—a condition that a trainee of Dr. Schur coined rhupus. In fact, physicians have often had to look toward medications used for other conditions to find some benefit for lupus patients. For example, hydroxychloroquine was originally developed as an antimalarial.
As knowledge about the interaction of lupus with related systemic conditions has grown, clinicians have realized that becoming pregnant is not the contraindication it once was. “We now know that it is safe for many, and we can much more easily predict complications by knowing autoantibody and renal function status,” he says.
Better Recognition of Lupus Classifications
“Fifty years ago, lupus was more or less a one-size-fits-all field,” Dr. Schur says. “Now, its extreme variability is recognized. Different guidelines for different scenarios are now the norm.”
Much of the bench work done by Dr. Schur and colleagues decades ago has led to easier and more convenient testing of lupus patients to help pinpoint disease specifics. The first lab test for the diagnosis, the LE cell prep, is long gone, replaced by better diagnostic tests, such as ANA and anti-DNA. The way these tests are done has shifted from labor-intensive, not very sensitive, immunodiffusion assays to automated solid-phase immunoassays that are more sensitive and highly reproducible. This includes stratification by clinical status, autoantibody, and complement, such that anti-DNA- and anti-Sm-positive patients with and without hypocomplementemia are known to be different from anti-Ro/SSA- and La/SSB-positive patients and different from antiphospholipid-positive patients, Dr. Schur says.
Similarly, many more ways exist for clinicians to assess disease activity, including the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM) and the European Consensus Lupus Activity Measurement (ECLAM), to name a few.
“Clinical trials are also using combinations of indices to create composite assessment measures for determining trial outcomes. Examples include the Systemic Lupus Erythematosus Response Index, used in the pivotal belimumab trails, and the BILAG-based Combined Lupus Assessment, used in a trial of epratuzumab,” Dr. Schur says.
Honing in on Pathogenesis
Researchers continue to examine lupus from different perspectives to hone in on its causes, Dr. Schur says. The study of genetics has become important for many conditions; although more than 50 genetic markers are associated with lupus, all are weak except certain genetic deficiencies of complement, Dr. Schur says. “Just because there’s a homozygous deficiency, it’s not clear how that’s affected clinical manifestations of the disease,” he says.
